Glucagon like-peptide-1-(7,36)-amide (GLP-1) suppresses glucagon release and increases the early phase of insulin secretion. However, it is currently controversial as to whether GLP-1 alters insulin sensitivity. Although it is well established that glucagon like-peptide-1-(7,36)-amide (GLP-1) is a potent stimulator of insulin secretion, its effects on insulin action and glucose effectiveness, subjects with type 2 diabetes were studied on two occasions. Insulin was infused during the night on both occasions to ensure that baseline glucose concentrations were comparable. On the morning of study, either GLP-1 (1.2 pmol/kg/min) or saline were infused along with somatostatin and replacement amounts of glucagon. Glucose also was infused in a pattern mimicking that typically observed following a carbohydarate meal while insulin concentrations either were varied so as to create a prandial insulin profile (n=6). The increase in glucose concentration was virtually identical on the GLP-1 and saline study days during prandial (0.56 +/- 0.14 vs. 0.56 +/- 0.10 Mol/L per 6 hrs) insulin infusion. Suppression of endogenous glucose production also was comparable on the GLP-1 and saline study dyas during prandial (-3.1 +/- 0.4 vs. -3.0 +/- 0.6 umol/kg) insulin infusion. Stimulation of glucose uptake in the presence or absence of GLP-1 was similar during prandial insulin infusion (1.9 +/- 0.2 vs. 2.2 +/- 0.3 mmol/kg). We conclude that wehn insulin and glucagon concentrations are matched, GLP-1 does not enhance glucose-induced stimulation of glucose uptake, glucose-induced suppression of glucose production. In addition, GLP-1 does not alter insulin action in people with type 2 diabetes.